Longitudinal analysis reveals transient immune impairment after LVAD implantation associated with Granzyme B+ CD8 effector memory T-cell reduction

Background: Left ventricular assist device (LVAD) implantation is an important treatment for end-stage heart failure. However, its impact on immune cell dynamics is still unclear, which potentially contributes to the high postoperative infection rate. Materials and Methods: We conducted a longitudinal multimodal analysis integrating clinical blood tests (n = 139, 2-year follow-up), single-cell RNA sequencing (scRNA-seq, n = 7, 5 time points), and flow cytometry (n = 20, 5 time points) to characterize the effects of LVAD implantation on immune cell counts, subset composition, and functional changes. Patient-derived peripheral blood mononuclear cells were used in in vitro experiments to validate the quantitative and functional alterations induced by the LVAD. Results: LVAD implantation induced a dramatic decrease in lymphocytes in the first week, which returned to preoperative levels by 2 months post-operation. Furthermore, flow cytometry and scRNA-seq data reveal that T cells are the lymphocytes with the most significant decrease after LVAD implantation. Notably, CD8-Tem-GZMB, a group of effector memory T cells that primarily perform cell killing and cytotoxic functions, declined significantly in the 2 weeks post-operation. Functional ELISpot assay indicates that the reduction in T-cell numbers manifests as an overall decrease in cytotoxic function. Mechanistically, apoptosis induced by shear stress exceeding the physiological range may contribute to T-cell depletion following LVAD implantation. An approximately 1.5-fold increase in the monocyte counts was observed in the first week post-operation and recovered by the first month, with decreased HLA-DR expression and antigen presentation function at 2 weeks postoperatively. NK cell counts and percentage declined significantly after LVAD implantation and did not recover until 3 months postoperatively. Conclusion: This study reveals a short-term impairment of cellular and innate immunity after LVAD implantation, which is associated with reduction in immune cell numbers and functional decline. This study provides a theoretical basis for monitoring the immune status and preventing potential infections after LVAD implantation.